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电针对银屑病小鼠血管生成的影响及机制研究OA北大核心CSTPCDMEDLINE

Effect of electroacupuncture intervention on angiogenesis in psoriasis mice

中文摘要英文摘要

目的:观察电针"足三里""血海"对咪喹莫特(IMQ)诱导的小鼠银屑病皮损组织血管生成的影响,探讨电针缓解银屑病皮损的机制.方法:选取24只雌性BALB/c小鼠,随机分为空白对照组、模型组、电针组,每组8只.模型组、电针组小鼠用5%IMQ乳膏对其背部皮肤进行涂抹以诱导银屑病模型;电针组小鼠在造模同时给予电针双侧"足三里""血海",1次/d,30 min/次,连续7 d.每天对小鼠背部皮损处皮肤拍照,采用银屑病面积和严重程度指数(PASI)进行评分,观察小鼠皮损动态变化;HE染色观察皮损组织形态学变化、表皮厚度及炎性细胞浸润程度;Masson染色观察并计算皮损组织胶原纤维占比;免疫组织化学法检测皮损组织微血管标志物CD31、血管内皮生长因子(VEGF)的阳性表达并计算微血管密度(MVD);Western blot法检测皮损组织中CD31、VEGF及丝裂原活化蛋白激酶(MAPK)信号通路相关蛋白p38、磷酸化(p)-p38、细胞外调节蛋白激酶(ERK)、p-ERK、c-Jun氨基末端激酶(JNK)、p-JNK的表达水平.结果:与空白对照组相比,模型组小鼠背部皮肤出现红斑、鳞屑、皮肤增厚症状,第7天红斑、鳞屑、皮肤增厚程度评分及总PASI评分升高(P<0.001),表皮明显增厚(P<0.001),胶原纤维占比、皮肤组织CD31及VEGF的MVD值、皮肤组织CD31、VEGF的蛋白表达水平及MAPK信号通路相关蛋白p-p38/p38、p-ERK/ERK、p-JNK/JNK比值明显升高(P<0.001,P<0.01).与模型组相比,电针组小鼠背部皮损明显改善,第7天红斑、鳞屑、皮肤增厚程度评分及总PASI评分显著下降(P<0.05,P<0.01),表皮厚度明显降低(P<0.001),皮损组织胶原纤维占比明显减少(P<0.01),皮损组织CD31、VEGF的MVD值、皮损组织CD31、VEGF的蛋白表达水平及MAPK信号通路相关蛋白p-p38/p38、p-ERK/ERK、p-JNK/JNK比值明显降低(P<0.05,P<0.001,P<0.01).结论:电针"足三里""血海"可改善IMQ诱导的小鼠银屑病样皮损改变,其作用机制可能是通过调控MAPK信号通路抑制皮损处血管生成相关因子CD31和VEGF的表达,从而改善银屑病皮损症状.

Objective To observe the effect of electroacupuncture(EA)stimulation of"Zusanli"(ST36)and"Xuehai"(SP10)on the angiogenesis of the local injured skin tissue in mice with psoriasis,so as to explore its mechanisms underlying improvement of psoriasis-induced skin lesions.Methods A total of 24 female BALB/c mice aged 6-8 weeks were randomly divided into control,model and EA groups,with 8 mice in each group.The psoriasis-like skin lesion model was established by application of 5%imiquimod(IMQ)cream to the mice's back skin,62.5 mg/d,for 7 days after local depilation,and the mice of the control group received local application of an equal amount of petroleum jelly once a day for 7 days.EA stimulation(2 Hz/100 Hz)was applied to ST36 and SP10 for 30 min,once daily for 7 consecutive days.Photos of the topical injured skin at the back were taken every day,and the severity of psoriasis lesions(psoriasis area and severity index[PASI])was scaled.Following H.E.staining,the morphological changes in the injured skin tissue were observed with epidermal thickness analyzed,and the Masson staining was used to observe the proportion of collagen fibers in the injured skin tissues.Immunohistochemical method was used to detect the expression of microvascular markers CD31 and vascular endothelial growth factor(VEGF)and the microvascular density(MVD)was calculated.Western blot was used to detect the expression levels of CD31,VEGF proteins and mitogen activated protein kinases(MAPK)signaling pathway related proteins p38,phosphorylated p38(p-p38),extracellular regulated protein kinases(ERK),p-ERK,c-Jun N-terminal kinase(JNK)and p-JNK in the injured skin tissue.Results Compared with the control group,the mice in the model group showed an evident increase in the erythema score,scales score,skin thickening score and PASI score,epidermal thickness,proportion of the collagen fibers,MVD value of CD31 and VEGF,and expression levels of CD31 and VEGF proteins,and p-p38/p38,p-ERK/ERK and p-JNK/JNK ratios in the injured skin tissue(P<0.001,P<0.01).In contrast to the model group,the EA group had a significant decrease in the levels of all the indexes mentioned above(P<0.05,P<0.01,P<0.001).Conclusion EA intervention can improve the psoriasis-like skin lesions induced by IMQ in mice,which may be related with its functions in down-regulating the expression of angiogenic related factors CD31 and VEGF proteins and MAPK signaling pathway related proteins in the topical injured skin tissue.

陈姣姣;陈泽斌;殷妮娜

湖北中医药大学,针灸骨伤学院,武汉 430065湖北中医药大学,基础医学院,武汉 430065

银屑病电针血管生成丝裂原活化蛋白激酶信号通路

PsoriasisElectroacupunctureAngiogenesisMitogen activated protein kinases signal pathway

《针刺研究》 2024 (006)

577-584 / 8

国家自然科学基金项目(No.81574055);湖北省自然科学基金项目(No.2022CFB190)

10.13702/j.1000-0607.20230379

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